Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease

TY - JOUR

T1 - Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease

AU - Cremer, Sebastian

AU - Pilgram, Lisa

AU - Berkowitsch, Alexander

AU - Stecher, Melanie

AU - Rieg, Siegbert

AU - Shumliakivska, Mariana

AU - Bojkova, Denisa

AU - Wagner, Julian Uwe Gabriel

AU - Aslan, Galip Servet

AU - Spinner, Christoph

AU - Luxán, Guillermo

AU - Hanses, Frank

AU - Dolff, Sebastian

AU - Piepel, Christiane

AU - Ruppert, Clemens

AU - Guenther, Andreas

AU - Rüthrich, Maria Madeleine

AU - Vehreschild, Jörg Janne

AU - Wille, Kai

AU - Haselberger, Martina

AU - Heuzeroth, Hanno

AU - Hansen, Arne

AU - Eschenhagen, Thomas

AU - Cinatl, Jindrich

AU - Ciesek, Sandra

AU - Dimmeler, Stefanie

AU - Borgmann, Stefan

AU - Zeiher, Andreas

AU - LEOSS study group

PY - 2021/10/21

Y1 - 2021/10/21

N2 - AIMS: Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity.METHODS AND RESULTS: We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59-0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43-0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators.CONCLUSION: These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.

AB - AIMS: Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity.METHODS AND RESULTS: We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59-0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43-0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators.CONCLUSION: These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Angiotensin Receptor Antagonists/administration & dosage

KW - Angiotensin-Converting Enzyme Inhibitors/administration & dosage

KW - Biomarkers/blood

KW - COVID-19/blood

KW - Comorbidity

KW - Disease-Free Survival

KW - Female

KW - Humans

KW - Hypertension/blood

KW - Inflammation/blood

KW - Male

KW - Middle Aged

KW - Registries

KW - SARS-CoV-2/metabolism

KW - Severity of Illness Index

KW - Survival Rate

U2 - 10.1371/journal.pone.0258684

DO - 10.1371/journal.pone.0258684

M3 - SCORING: Journal article

C2 - 34673795

VL - 16

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 10

M1 - e0258684

ER -